EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITORS, L-NG-NITROARGININE AND L-NG-NITROARGININE METHYL-ESTER, ON RESPONSES TO VASODILATORS OF THE GUINEA-PIG CORONARY VASCULATURE

1 The effects of L-N(G)-nitroarginine (L-NOARG) and L-N(G)-nitroarginine methyl ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2 The vasodilator responses evoked by low doses of 5-HT (5 x 10(-10) - 5 x 10(-8) mol) were almost abolished by L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) and 10(-4) M), althoUgh L-NOARG (3 x 10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3 The vasodilator responses evoked by substance P (5 x 10(-12) - 5 x 10(-9) mol) were reduced in the presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4 The amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9) - 5 x 10(-7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) m). However, the area of the response to ATP (5 x 10(-10) - 5 X 10(-7) mol) was inhibited by L-NAME (10(-5), 3 x 10(-5) and 10(-4) M) and to a lesser extent by L-NOARG (10(-5) and 10(-4) M). 5 The amplitude and area of the vasodilator responses to bradykinin (5 x 10(-12) - 5 x 10(-11) mol) were reduced, but not abolished, by L-NOARG and L-NAME. 6 Neither the amplitude nor area of the responses to sodium nitroprusside (5 x 10(-10) -5 x 10(-7) mol) were inhibited by either L-NAME or L-NOARG (both at 10(-5) and 3 x 10(-5) m). 7 It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the vasodilator actions of 5-HT and ATP in this preparation.